1. Field of the Invention
The present invention relates to novel 1,2,3,4-tetrahydroquinoxaline derivatives which have, as a substituent, a phenyl group having a sulfonic acid ester structure or a sulfonic acid amide structure introduced therein or a salt thereof, which are useful as pharmaceuticals. The derivatives have a glucocorticoid receptor binding activity and are useful as glucocorticoid receptor modulators having a nonsteroidal structure (glucocorticoid receptor agonists and/or glucocorticoid receptor antagonists).
2. Description of the Related Art
A glucocorticoid receptor is a 94 kDa ligand-activated intracellular transcriptional regulatory factor that is a member of the nuclear receptor superfamily. This receptor is known to affect the regulation of the metabolism of carbohydrates, proteins, fats and the like, suppression of the immune or inflammatory responses, activation of the central nervous system, regulation of cardiovascular function, and basal and stress-related homeostasis and the like due to it transcriptional regulatory action. As diseases which are considered to be related to glucocorticoid receptor, metabolic disorders such as diabetes and obesity, inflammatory diseases such as enteritis and chronic obstructive pulmonary diseases, autoimmune diseases such as connective tissue diseases, allergic diseases such as asthma, atopic dermatitis and allergic rhinitis, central nervous system diseases such as psychiatric disorders, Alzheimer's disease and drug use disorders, cardiovascular diseases such as hypertension, hypercalcemia, hyperinsulinemia and hyperlipidemia, homeostasis-related diseases causing an abnormality of neuro-immune-endocrine balance, glaucoma and the like are known (SOUGOU RINSYOU, 54(7), 1951-2076 (2005), JP-A-2002-193955).
Therefore, it is considered that a compound having a glucocorticoid receptor binding activity is useful as preventive and/or therapeutic agent for these diseases.
As such a compound having a glucocorticoid receptor binding activity, glucocorticoid receptor agonists synthesized in the living body such as cortisol and corticosterone, synthetic glucocorticoid receptor agonists such as dexamethasone, prednisone and prednisilone, non-selective glucocorticoid receptor antagonists such as RU486 and the like are known (JP-A-2002-193955).
On the other hand, compounds having a 1,2,3,4-tetrahydroquinoxaline structure are disclosed in WO 2004/099192, JP-A-5-148243 and the like. The compounds disclosed in WO 2004/099192 relate to protein thyrosine phosphatase inhibitors essentially having a carboxylic group. A very large number of compounds having 1,2,3,4-tetrahydroquinoxaline structure and the use of them as anti-virus agents are disclosed in JP-A-5-148243. However, 1,2,3,4-tetrahydroquinoxaline derivatives which have, as a substituent, a phenyl group having a sulfonic acid ester structure or a sulfonic acid amide structure introduced therein or a salt thereof have not been specifically disclosed in any of literatures.